Method and system for generating and collecting a radionuclide eluate

ABSTRACT

A method and system for filling a vial with an eluate containing a radionuclide by coupling a vial containing a prepackaged amount of eluant to both an inlet to a radionuclide generator column and a vent outlet and coupling an evacuated vial to an outlet from the radionuclide column. The method and system may utilize a filter which includes an eluate repellent portion.

[ Nov. 20, 1973 [5 METHOD AND SYSTEM FOR GENERATING 3,369,121 2/1968 Bruno et al. 250/106 T Primary ExaminerArchie R. Borchelt Att0rney-Sewall P. Bronstein et al.

[75] Gerald J. Litt, Wellesley, Mass. [73 Assignee: New England Nuclear Corporation,

Boston. Mass.

July 12, 1971 ABSTRACT [22] Filed:

[ PP N03 161,761 A method and system for filling a vial with an eluate containing a radionuclide by coupling a vial contain- [52] Us. 51 250/108 R ing a prepackaged amount of eluant to both an inlet to 25O/43'5 252/3011 R a radionuclide generator column and a vent outlet and 51 1m. (:1. G21h 5/02 evacuated the radio nuclide column. The method and system may utilize a filter which includes an eluate repellent portion.

[58] Field of Search..................... 250/106 S, 106 T,

12 Claims, 6 Drawing Figures [56] References Cited UNITED STATES PATENTS 3,576,998 5/1971 Deutsch et a1. 250/l06 T PATENTEDHBV20 1915 3774.035

SHEET 2 OF 2 METHOD AND SYSTEM FOR GENERATING AND COLLECTING A RADIONUCILTDE ELUATE BACKGROUND OF THE INVENTION This invneion relates to the generation of radionuclides and more particularly to a new and improved method and system for generating and collecting radionuclides for use in nuclear medicine.

For an explanation of the uses of radionuclides, reference may be had to U.S. Pat. Ser. No. 3,576,998 issued to Deutch, Mead and Nagy on May 4, 1971. In the past, radionuclides have been collected using an evacuated collecting tube or the like which is coupled to an outlet needle provided at the end of a tube connected to a radionuclide generating column. Eluant is passed into the column to generate an eluate containing the radionuclide. The eluant is generally a saline solution. As shown in the aforementioned patent, eluant for generating the eluate has been provided by a large bag containing a large amount of eluant.

in another system sold by Abbott Laborotories, the eluant is provided from an intravenous type bottle and is used to fill a smaller chamber to provide an amount of eluant sufficient to form an amount of eluate to fill a container.

With this system, the smaller chamber is coupled by I a first valve to the inlet of the column and the smaller chamber is coupled to the larger bottle by a second valve. Thus, to use this system, the larger bottle has to be held in a manner so that the valves can be manipulated and opened sequentially to permit eluant to be fed into the column.

Although both of said above identified systems have proven to be quite useful, additional convenience in use was desired by those having to use radionuclide generators on a day to day basis. Accordingly, there had developed a need for a new and improved method and system for generating eluate in a simple and convenient manner in which few manipulations are required to generate the eluate.

The above has now been accomplished in a new and improved manner by using sealed vials containing prepackaged amounts of eluant which may be directly coupled to an inlet of the generator column and simultaneously using evacuated vials suitably sealed which are coupled to the outlet of the generator column.

it has also been found that with this new and improved system, that the column may be dried if desired to increase column efficiency by using evacuated vials which are sufficiently evacuated and of sufficient volume to not only draw the eluate generated by the eluant into it, but to also draw air from the eluant containing vial through the column after the eluant has been dispensed. In this embodiment, air is fed into the eluant containing bottle by a vent which in the preferred embodiment includes a needle adapted to be inserted into the eluant containing vial at the same time the eluant containing vial is coupled to the inlet of the column.

As another feature of this invention, there is provided a new and improved filtering means to filter the eluate after it leaves the column. Heretofore, filters capable of removing submicron particles such as bacteria would retard the passage of air therethrough. The new and improved filtering means facilitates the flow of air to dry the column after the eluate has been collected in the evacuated vial. In particular, the new and improved filtering means includes an eluate repellant portion to permit the passage of air therethrough after the eluate has been filtered by another portion of the filtering means. In its most preferred form the filtering means includes a disc having an eluate repellent rim.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a perspective view with parts broken away of a self contained unit for generating radionuclide substances in accordance with the invention;

FIG. 2 is a diagrammatic view showing one step in the generation of a radionuclide substance in accordance with the invention;

FIG. 3 shows in diagrammatic form the filtering means used in this invention;

FIG. 4 shows a top view of the disc portion of the filter of FIG. 3; and

FIG. 5 and FIG. 6 show diagrammatically the production of eluate containing a radionuclide according to the invention.

Reference should now be had to FIG. 1 for a brief description of the construction of a radionuclide generator 10 according to the invention.

The generator 10 comprises an outer container 11 (e.g. of metal), an internal spacer 12 (e.g. of plastic foam) shaped to support the parts of the generator, and a lid 13 (e.g. of plastic) having a charge well 14 and a collect well 15 formed therein.

Within the radionuclide generator 10, a supply of a desired daughter radionuclide is available in a chamber or column 16 (shown dotted in FIG. 1) which is conventional in the art and is described more fully in US. Pat. No. 3,576,998, the entire disclosure of which is incorporated herein.

The daughter radionuclide may be for example, radioactive technetium (Tc-99m) which is generated by radioactive molybdenum-99, as obtained from a nuclear reactor. Since the column 16 contains radioactive materials, it is encased by a shield, or pig 17 (shown dotted in FIG. 11) of lead.

The column 16 is coupled through tubes 20 and 21 to tube connectors 22 and 23 respectively. The connector 22 is then coupled via a tube 24 to a filter 25 (which will be more fully described) which in turn is coupled via tube 26 to a plug 27 having an inlet and outlet, the inlet being a tube 28 and the outlet being a needle 29 with an opening at the top. The needle is used as will be described for piercing through a seal of an evacuated vial or bottle and extending into the interior thereof to facilitate the flow of eluate into the vial.

In order to supply eluant to the column there is provided a tube 30 coupled to connector 23 and to a plug 31. The plug 31 supports first and second needles 32 and 33. The needle 32 has an opening at the top for passage of eluant, e.g. a saline solution .9 percent NaCl), prepackaged in a vial or bottle having a pierceable seal. The needle 32 is positioned in the well 14 such that is is adapted to pierce the seal of the vial and enter into the interior of the vial. The eluant is then fed into an outlet tube 34 and into the tube 30. The second needle 33 has an opening at the top and is also positioned in the well such that it too may be inserted into the interior of the vial through the seal thereof in order to permit the flow of air into the vial.

The second needle forms part of a vent which includes an outlet tube 35 coupled to a tube 36 which in turn is connected to an antibacterial plug 37 having a sterile barrier 38 (e.g. cotton) at the top thereof.

Reference should now be had to FIGS. 2, 5 and 6 for an explanation of the operation of the generator according to the invention.

At 40 there is shown a charge vial having a needle pierceable seal 41 (e.g. a rubber septum seal) at the top thereof supported by a cap 42 attached to the vial top and which contains a prepackaged and predetermined amount of eluant 43. The eluant is generally a sterile saline solution as aforementioned which selectively eluates the daughter radionuclide as it is passed through the column 16. The vial is placed over both of the needles 32 and 33 as shown in FIGS. 2, 5 and 6 so that the needles extend into the interior thereof to permit the eluant to flow into the column and at the same time to permit air to enter the vial 40 via the vent outlet needle 33.

In order to draw the eluant through the column there is provided a sealed preevacuated and sterile collecting or eluate vial 50 having a needle pierceable seal 51 supported by a cap 52 affixed to the top of the vial 50.

The vial 50 is placed over the needle 29 so that it extends into the interior thereof. The vial St) is preferably evacuated to about 42 to 44 or less millimeters of mercury, and will pass an electrical discharge in accordance with a conventional spark coil test.

In the most preferred embodiment of this invention, the prepackaged volume of the eluant in vial 40 is of an amount so that it preferably does not completely fill the evacuated vial 50 after it becomes an eluate by passing through the column. Thus there remains sufficient vacuum (excess vacuum capacity) to draw air from the vial 40 after it has been emptied of eluant to the level of the needles 32 and 33 positioned therein. The passage of air through the column aids in drying the column which has been found to increase significantly the efficiency and reproducibility of the system.

In the preferred embodiment of the invention, the vial 40 used contains 21 ml of saline (eluant) and the vial St is an evacuated vial and the eluate collection vial has a volume capacity of 27 ml. The exact volume of the collection vial is immaterial so long as it has sufficient capacity to draw eluant through the column, the eluate from the column into it and then draw air through the column to dry it.

As another feature of this invention there is provided a new and improved filter for filtering the eluate. The filter 25 is shown more particularly in FIGS. 3 and 4 and comprises an inlet 25a, an outlet 25b, a housing 256 and a filtering disc 25d. The disc 25d comprises a plurality of holes spirally extending from the top surface thereof (inlet side) to the bottom surface thereof (outlet side). The preferred filter holes are adapted to pass fluids therethrough and are particularly used in this invention to filter out alumina which is present in the column and thus in the eluate.

The preferred filter has holes 0.22 microns in diameter. However, if the filter is not used to trap bacteria but only fine particles of alumina, the holes can be slightly larger (e.g. l to .45 microns). In addition, the filter disc 25d includes a hydrophobic rim or edge 25e which is adapted to act as an eluate repellent.

The edge may be prepared by coating the surface of the filter with a material such as dichloro dimethyl silane. In this manner the eluant is prevented from clogging the holes of the edge and thus air may be passed through the filter to dry the column after passage of the eluate therethrough. A hydrophobic filter of the type suitable for use in this invention may be purchased from the Millipore Corporation, Bedford, Massachusetts and are marked with U.S. Pat. No. 3,471,019.

Briefly, the operation of the method is as follows: the bottle 40 filled with a saline solution is placed over needles 32 and 33 as shown in FIG. 5. Thereafter the evacuated vial 50 is placed over needle 29 to draw the eluant through the column and then air through the column. FIG. 6 shows the eluate after it has been transferred to vial 50.

I claim:

ll. In a method of generating an eluate containing a desired daughter radionuclide by flowing an eluant, which is selectively solvent of said daughter radionuclide to form said eluate, from a source of said eluant through an inlet to and through a column containing a parent radionuclide which spontaneously decays into said daughter radionuclide, and from said column to an outlet, the improvement comprising coupling to said inlet in a closed fashion the interior of a sealed eluant vial containing a predetermined and prepackaged amount of said eluant and then coupling in a closed fashion to said outlet the interior of a sealed, evacuated eluate collecting vial to thereby automatically draw said eluate out of said eluant vial through said column and out of said outlet into said evacuated eluate vial by the vacuum in said evacuated vial, said improvement also comprising said sealed eluant vial containing an amount of eluant insufficient to fill said evacuated eluate vial and the eluate vial being of sufficient volume and being sufficiently evacuated so that air is drawn through said column after said eluant vial and column have been emptied of eluant to thereby dry said column for the next eluation.

2. A method according to claim 1 wherein the eluate is filtered as it is discharged from the column through a filtering means, said air also being drawn through said filtering means after said eluant vial and column have been emptied and said eluate has been passed through said filter, and wherein a portion of said filtering means is hydrophobic to the eluate to thereby reduce resistance to flow of said air therethrough so that said air can be drawn through and from said column and filter by the reduced vacuum in said eluate vial after the eluant vial and column have been emptied and the eluate has been passed through said filtering means.

3. A method according to claim I wherein said vials both have pierceable seals, wherein the evacuated eluate vial is coupled to said outlet by impaling its pierceable seal on outlet needle means in communication with said outlet and wherein the eluant vial is coupled to said inlet by impaling its pierceable seal onto inlet needle means to put the interior of said eluant vial in communication with said inlet and with a vent to the atmosphere through a sterile plug, whereby an eluate sample can be obtained in said eluate vial followed by drying the column for the next eluation merely by impaling said vials on said needle means.

4. A radionuclide generator system for generating a relatively short lived daughter radionuclide from a long lived parent radionuclide, which is spontaneously decayable into said short lived daughter radionuclide, comprising a generator column containing said parent radionuclide and said daughter radionuclide, said column having a column inlet means for inletting an eluant for said daughter radionuclide to form an eluate of said daughter radionuclide in said eluant and a column outlet means for outletting said eluate, said system also including a vent supported by said generator and positioned next to said inlet means, needle means associated with said inlet means and vent and mounted on said generator, said needle means being exposed so that the pierceable seal of a sealed eluant vial may be impaled on said needle means to thereby couple the interior of said eluant vial with said column and with said vent to vent said interior to the atmosphere, said column outlet means including needle means exposed for penetrating a pierceable seal of an evacuated eluate vial, said system including said eluant vial which contains a prepackaged and predetermined amount of eluant, said system also including said evacuated eluate vial, the amount of eluant in the eluant vial being insufficient to fill up the eluate vial and the amount of vacuum in said eluate vial being such that air is drawn through said vent and column into the eluate vial by the remaining vacuum in said eluate vial to dry said column after the eluant has been emptied from said eluant vial by the vacuum in said eluate vial.

5. A radionuclide generator system for generating a relatively short lived daughter radionuclide from a long lived parent radionuclide, which is spontaneously decayable into said short lived radionuclide comprising a generator column containing said parent radionuclide and said daughter radionuclide, said column having a column inlet means for inletting an eluant for said daughter radionuclide to form an eluate of said daughter radionuclide in said eluant and for inletting air to vent said system during eluation and to dry said column between eluations and column outlet means for outletting said eluate during eluations and air after each eluation, said eluate, during eluation, and said air, after said eluation, being drawn into said inlet and through said column by coupling to said outlet means a sealed evacuated eluate vial and filtering means positioned after said column for filter sterlizing said eluate, said filtering means including a portion thereof which is hydrophobic to the eluate so that air can be drawn through the filter by the reduced vacuum in said eluate vial to dry said column after a predetermined amount of the eluate has been drawn by the vacuum in said eluate vial thorugh said column, through another portion of the filter and into said eluate vial.

6. A method according to claim 1, said air being inletted into said eluant vial through a sterile plug to provide sterile venting of said eluant vial during eluation and to provide a source of said air for drying said column after said eluation.

7. A method according to claim 3, said inlet needle means comprising a pair of needles one of which is in communication with said inlet and the other of which is in communication with said vent to the atmosphere, said eluant vial being coupled to said inlet and being vented to the atmosphere by impaling said pierceable seal thereof on said pair of needles, said vent venting said eluant vial to the atmosphere during eluation of the eluant vial and providing a source of air for drying said column after said eluation.

8. A system according to claim 4, said system also including filtering means between said column and said column outlet means for filtering said eluate, said air being drawn through said filtering means by said remaining vacuum.

9. A system according to claim 8, said needle means associated with said inlet means and vent comprising a first inlet needle mounted on said generator in communication with said column and forming a part of said inlet means and a second vent needle forming part of said vent and located next to said first needle, both said needles being exposed so that said pieceable seal of said eluant vial is impaled on both said needles.

10. A system according to claim 8, including a plurality of said eluant vials and a plurality of said eluate vials for a plurality of eluations, the pierceable seal of each eluant vial being impaled on said inlet needle and said vent needle followed by impaling the pierceable seal of an eluate vial on said outlet needle means to automatically achieve an eluation with drying of the column after such eluation.

11. A system according to claim 8, said inlet needle and vent needle being mounted in a well at the top of the generator and said outlet needle means being mounted in another well at the top of said generator.

12. A system according to claim 9, said filtering means including a portion which is hydrophobic to said eluate to reduce resistance to flow of air therethrough by the reduced vacuum in said eluate vial after the eluant vial and column have been emptied and said eluate has passed through said filtering means. 

1. In a method of generating an eluate containing a desired daughter radionuclide by flowing an eluant, which is selectively solvent of said daughter radionuclide to form said eluate, from a source of said eluant through an inlet to and through a column containing A parent radionuclide which spontaneously decays into said daughter radionuclide, and from said column to an outlet, the improvement comprising coupling to said inlet in a closed fashion the interior of a sealed eluant vial containing a predetermined and prepackaged amount of said eluant and then coupling in a closed fashion to said outlet the interior of a sealed, evacuated eluate collecting vial to thereby automatically draw said eluate out of said eluant vial through said column and out of said outlet into said evacuated eluate vial by the vacuum in said evacuated vial, said improvement also comprising said sealed eluant vial containing an amount of eluant insufficient to fill said evacuated eluate vial and the eluate vial being of sufficient volume and being sufficiently evacuated so that air is drawn through said column after said eluant vial and column have been emptied of eluant to thereby dry said column for the next eluation.
 2. A method according to claim 1 wherein the eluate is filtered as it is discharged from the column through a filtering means, said air also being drawn through said filtering means after said eluant vial and column have been emptied and said eluate has been passed through said filter, and wherein a portion of said filtering means is hydrophobic to the eluate to thereby reduce resistance to flow of said air therethrough so that said air can be drawn through and from said column and filter by the reduced vacuum in said eluate vial after the eluant vial and column have been emptied and the eluate has been passed through said filtering means.
 3. A method according to claim 1 wherein said vials both have pierceable seals, wherein the evacuated eluate vial is coupled to said outlet by impaling its pierceable seal on outlet needle means in communication with said outlet and wherein the eluant vial is coupled to said inlet by impaling its pierceable seal onto inlet needle means to put the interior of said eluant vial in communication with said inlet and with a vent to the atmosphere through a sterile plug, whereby an eluate sample can be obtained in said eluate vial followed by drying the column for the next eluation merely by impaling said vials on said needle means.
 4. A radionuclide generator system for generating a relatively short lived daughter radionuclide from a long lived parent radionuclide, which is spontaneously decayable into said short lived daughter radionuclide, comprising a generator column containing said parent radionuclide and said daughter radionuclide, said column having a column inlet means for inletting an eluant for said daughter radionuclide to form an eluate of said daughter radionuclide in said eluant and a column outlet means for outletting said eluate, said system also including a vent supported by said generator and positioned next to said inlet means, needle means associated with said inlet means and vent and mounted on said generator, said needle means being exposed so that the pierceable seal of a sealed eluant vial may be impaled on said needle means to thereby couple the interior of said eluant vial with said column and with said vent to vent said interior to the atmosphere, said column outlet means including needle means exposed for penetrating a pierceable seal of an evacuated eluate vial, said system including said eluant vial which contains a prepackaged and predetermined amount of eluant, said system also including said evacuated eluate vial, the amount of eluant in the eluant vial being insufficient to fill up the eluate vial and the amount of vacuum in said eluate vial being such that air is drawn through said vent and column into the eluate vial by the remaining vacuum in said eluate vial to dry said column after the eluant has been emptied from said eluant vial by the vacuum in said eluate vial.
 5. A radionuclide generator system for generating a relatively short lived daughter radionuclide from a long lived parent radionuclide, which is spontaneously decayable into said short lived radionuclide Comprising a generator column containing said parent radionuclide and said daughter radionuclide, said column having a column inlet means for inletting an eluant for said daughter radionuclide to form an eluate of said daughter radionuclide in said eluant and for inletting air to vent said system during eluation and to dry said column between eluations and column outlet means for outletting said eluate during eluations and air after each eluation, said eluate, during eluation, and said air, after said eluation, being drawn into said inlet and through said column by coupling to said outlet means a sealed evacuated eluate vial and filtering means positioned after said column for filter sterlizing said eluate, said filtering means including a portion thereof which is hydrophobic to the eluate so that air can be drawn through the filter by the reduced vacuum in said eluate vial to dry said column after a predetermined amount of the eluate has been drawn by the vacuum in said eluate vial thorugh said column, through another portion of the filter and into said eluate vial.
 6. A method according to claim 1, said air being inletted into said eluant vial through a sterile plug to provide sterile venting of said eluant vial during eluation and to provide a source of said air for drying said column after said eluation.
 7. A method according to claim 3, said inlet needle means comprising a pair of needles one of which is in communication with said inlet and the other of which is in communication with said vent to the atmosphere, said eluant vial being coupled to said inlet and being vented to the atmosphere by impaling said pierceable seal thereof on said pair of needles, said vent venting said eluant vial to the atmosphere during eluation of the eluant vial and providing a source of air for drying said column after said eluation.
 8. A system according to claim 4, said system also including filtering means between said column and said column outlet means for filtering said eluate, said air being drawn through said filtering means by said remaining vacuum.
 9. A system according to claim 8, said needle means associated with said inlet means and vent comprising a first inlet needle mounted on said generator in communication with said column and forming a part of said inlet means and a second vent needle forming part of said vent and located next to said first needle, both said needles being exposed so that said pieceable seal of said eluant vial is impaled on both said needles.
 10. A system according to claim 8, including a plurality of said eluant vials and a plurality of said eluate vials for a plurality of eluations, the pierceable seal of each eluant vial being impaled on said inlet needle and said vent needle followed by impaling the pierceable seal of an eluate vial on said outlet needle means to automatically achieve an eluation with drying of the column after such eluation.
 11. A system according to claim 8, said inlet needle and vent needle being mounted in a well at the top of the generator and said outlet needle means being mounted in another well at the top of said generator.
 12. A system according to claim 9, said filtering means including a portion which is hydrophobic to said eluate to reduce resistance to flow of air therethrough by the reduced vacuum in said eluate vial after the eluant vial and column have been emptied and said eluate has passed through said filtering means. 